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Search for HIV vaccine faces setback

Scientists from Britain and the US, who published their findings in Nature, have investigated 114 viral sequences from all eight major subtypes of HIV from around the world.

At least 10 of the viruses had "mosaic" sequences representing a hybrid virus that had evolved within a single patient infected by two distinct strains of HIV. All eight subtypes had been found to contain hybrids, clearly showing that the phenomenon was a universal problem that involved one virus swapping its genes with those of another infecting the same human cell.

Only a year ago such recombination was thought to be so unlikely as to be practically impossible. The researchers believe, however, that coinfection with two or more strains of HIV is almost certainly underestimated by their findings "since recombinants of divergent viruses from the same sequence subtype are much more difficult to detect."

The research team, drawn from Nottingham University; the Walter Reed Army Institute of Research in Rockville, Maryland; and the University of Alabama at Birmingham, said that the findings emphasise the importance of looking for hybrid HIV strains in countries such as Thailand where vaccine programmes are planned.

"The surprisingly high frequency of mosaic HIV-1 sequences in the database implies that a substantial proportion of individuals can become coinfected with HIV-1 strains belonging to different sequence subtypes, and that recombination between these genomes can occur in vivo to generate bilogically active viruses."

The researchers added: "These results raise pressing questions concerning global frequency of such recombinants, their biological significance, and their impact on vaccine design and development. They prompt investigation of the circumstances under which coinfection (either by simultaneous transmission of divergent viruses, or by successive superinfection) can occur."

One of the more intriguing and potentially worrying aspects of hybrid strains is that they could result in the evolution of a type of HIV that possesses significantly greater pathogenic qualities, such as higher transmissibility.

Professor Paul Sharp, professor of genetics at Nottingham University, said that this was one of the great unknowns at present. "I would not want to create a scare, but this ability to create hybrids gives you an evolutionary jump and we don't know what the properties of a hybrid may be."

The ability to recombine within human cells, he said, "is another worrying complication" to the already diverse nature of the virus.

Genetic recombination in other viruses has been known to make them dangerous. For instance, scientists have shown that two non-pathogenic strains of herpes virus can produce a pathogenic hybrid that can kill laboratory mice. Similarly, far more virulent flu viruses can come about after recombination between two relatively non-pathogenic forms.--STEVE CONNOR, science correspondent, Independent

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